Tele nucleophilic aromatic substitutions in 1-nitro-3- and 1,3-dinitro- 5-trichloromethylbenzene, and 3-trichloromethylbenzonitrile. A new synthesis of the 1,4-benzothiazine-3(4H)-one ring system from 3 nitrobenzoic acid

Article abstract of DOI:10.1016/S0040-4020(99)01012-1

3-Trichloromethylnitrobenzene 2, 1,3-dinitro-5-trichloromethylbenzene 13 and 3-trichloromethylbenzonitrile 18 react with sodium methoxide to give 4- methoxy-3-nitrobenzaldehyde 6, 4-methoxy-3,5-dinitrobenzaldehyde 15 and 5- dimethoxymethyl-2-methoxybenzonitrile 19, respectively. Compounds 2 and 13 react with methyl thioglycolate to afford dichloromethylacetates 7 and 16, respectively. These products are the result of tele nucleophilic aromatic substitution. Compound 18 reacted with methyl thioglycolate to give acetate 20 resulting from nucleophilic displacement of cyanide. Reductive cyclisation of 7 afforded benzothiazine 11. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01012-1

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 447–453
Tele Nucleophilic Aromatic Substitutions in 1-Nitro-3-
and 1,3-Dinitro-5-trichloromethylbenzene, and
3-Trichloromethylbenzonitrile. A New Synthesis of the
1,4-Benzothiazine-3(4H)-one Ring System from
3-Nitrobenzoic Acid
Thomas Giannopoulos,a John R. Ferguson,b Basil J. Wakefieldb and George Varvounisa,
*
aDepartment of Chemistry, University of Ioannina, 451 10, Ioannina, Greece
bUltrafine, Synergy House, Guildhall Close, Manchester M15 6SY, England, UK
Received 3 September 1999; revised 25 October 1999; accepted 11 November 1999
Abstract—3-Trichloromethylnitrobenzene 2, 1,3-dinitro-5-trichloromethylbenzene 13 and 3-trichloromethylbenzonitrile 18 react with
sodium methoxide to give 4-methoxy-3-nitrobenzaldehyde 6, 4-methoxy-3,5-dinitrobenzaldehyde 15 and 5-dimethoxymethyl-2-methoxy-
benzonitrile 19, respectively. Compounds 2 and 13 react with methyl thioglycolate to afford dichloromethylacetates 7 and 16, respectively.
These products are the result of tele nucleophilic aromatic substitution. Compound 18 reacted with methyl thioglycolate to give acetate 20
resulting from nucleophilic displacement of cyanide. Reductive cyclisation of 7 afforded benzothiazine 11. ᭧ 2000 Elsevier Science Ltd. All
rights reserved.
Nucleophilic aromatic substitution in carbocyclic and
heterocyclic arenes is a very important reaction from both
the academic and industrial point of view. Although the
classical SNAr reaction of aryl halides by addition-elimina-
tion has dominated the scene for over a century,1–5 reactions
following a different pathway have gained increasing inter-
est and importance. These can be grouped into the following
categories: elimination–addition (via arenes),6 single elec-
tron transfer promoted (SRN1) reactions,7 photochemical
reactions,8 transition metal catalysed reactions,9 nucleo-
philic ring opening and ring closure (ANRORC) reactions,10
and more recently, vicarious nucleophilic substitution
(VNS) of hydrogen,11,12 cine nucleophilic substitution13,14
and tele nucleophilic substitution.15–18
The requisite for these reactions is a trichloromethyl
group beta to the ring nitrogen of pyridine. Thus reaction
occurs by addition of nucleophile to the 6-position, elimina-
tion of chloride ion and a 1,5-hydrogen shift from the
6-position to the exocyclic carbon leading to a 2-substi-
tuted-5-dichloromethylpyridine. The final products depend
on the reaction conditions and work-up procedure, for
example with alkoxides they can be acetals or aldehydes
(Scheme 1).
Herein we report the reactions of 1-nitro-3-trichloromethyl-
benzene 2, 1,3-dinitro-5-trichloromethylbenzene 13
and 3-trichloromethylbenzonitrile 18 with sodium
methoxide and methyl thioglycolate. The products 6, 7, 9,
15 and 19 are the result of tele nucleophilic aromatic
substitution. The novel synthesis of benzothiazine 11 is
also reported.
We have previously reported several examples of tele
nucleophilic substitution in 3-trichloromethylpyridines.16,17
Scheme 1.
Keywords: benzenes; reduction; benzothiazines.
* Corresponding author. E-mail: gvarvoun@cc.uoi.gr
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01012-1

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T. Giannopoulos et al. / Tetrahedron 56 (2000) 447–453
Compound 2 was prepared in no more than 50% yield by
heating 3-nitrobenzoic acid 1 in a mixture of phenyl-
phosphonic dichloride and phosphorus pentachloride. This
method is described by McKendry et al.19c in a patent but
spectroscopic and analytical data are not given. Other
methods of preparing 2 are nitration of trichloromethyl-
benzene19a and Friedel–Crafts alkylation of 1-nitro-3-
trifluoromethylbenzene.19b The reaction of 2 with one
equivalent of sodium methoxide in boiling methanol gave
a mixture containing ester 4 (23%) and aldehyde 6 (59%),
implying that reaction occurs via the dichloromethoxy-
methyl compound 3 and the acetal 5, respectively, followed
by hydrolysis (Scheme 2). This is a rare case of competition
between an SN2 reaction and tele nucleophilic aromatic
substitution. Compound 6 has previously been prepared
by oxidation of (4-methoxy-3-nitrophenyl)methanol,20
methylation of 4-hydroxy-3-nitrobenzaldehyde,21 nitration
of 4-methoxybenzaldehyde22 and nucleophilic aromatic
substitution of chloride ion from 4-chloro-3-nitrobenzalde-
hyde.21a Compound 4 is commercially available.
work-up, gave 7 in 67% yield, with only 18% of starting
material 2.
Nitro-ester 7 is potentially a precursor to both benzo[2,3-
b]thiazole-N-oxide and 3,4-dihydro-2H-1,4-benzothiazin-3-
one ring systems. In a first attempt to cyclise 7 to the former
ring system we used triethylamine in ethanol under reflux,23a
only to recover starting material. In a second attempt,
compound 7 was heated in a methanolic solution of sodium
methoxide.23b Instead of the hoped-for cyclisation product,
acetal 10 was obtained. On the other hand, reaction of 7 with
zinc and calcium chloride in aqueous methanol gave 11 in
52% yield. This three step synthesis of a 3,4-dihydro-2H-
1,4-benzothiazin-3-one from 3-nitrobenzoic acid by sequen-
tial chlorination, tele nucleophilic aromatic substitution
and reductive cyclisation constitutes a novel route to this
ring system. Other syntheses of this ring system are reduc-
tive cyclisation of 4-acetyl-2-nitrophenylthioacetic acid
with ferrous sulfate-ammonium hydroxide,24 reaction of
o-aminobenzenethiols with 2,4-oxetanedione,25 treatment
of zinc salts of o-aminobenzenethiols with chloroacetyl
chloride,26 reaction of N,N0-dialkyldithiodianilines with
b-keto esters27 and more recently by reductive cyclisation
of (2-nitrophenylsulfanyl)acetic acids.28
The outcome of the reaction of compound 2 with methyl
thioglycolate (Scheme 3) depended on the reaction con-
ditions. With methanol as solvent, 2 was heated under
reflux with methyl thioglycolate and either triethylamine
or potassium carbonate. When triethylamine was used
followed by dry work-up, dichloromethyl compound 7 and
starting material were isolated in 31 and 23% yield, respec-
tively. When potassium carbonate was used followed by
aqueous work-up, 7, 9 and starting material were isolated
in 12, 27 and 30% yield, respectively. The isolation of
aldehyde 9 implies that reaction occurs via thioacetal 8
which was hydrolysed during work-up. On the other
hand, a reaction in DMF at ambient temperature with
HMPA as catalyst and triethylamine, followed by aqueous
The preparation and reactions of 1,3-dinitro-5-trichloro-
methylbenzene 13 are shown in Scheme 4. It was prepared
by heating 3,5-dinitrobenzoic acid 12 with phenylphos-
phonic dichloride and phosphorus pentachloride. Smith
et al.29 prepared 13 by heating 1,3-dinitro-5-trifluoromethyl-
benzene in acetyl chloride containing anhydrous aluminium
chloride. Reaction of 13 with methanolic sodium methoxide
at room temperature for 24 h afforded the aldehyde 15.
Since water was excluded during the synthesis and work-
up of this compound, it is proposed that acetal 14 was an
Scheme 2. Reagents: (a) PhP(O)Cl2, PCl5; (b) MeONa, MeOH, reflux; (c) H2O.

T. Giannopoulos et al. / Tetrahedron 56 (2000) 447–453
449
Scheme 3. Reagents: (a) HSCH2CO2Me, K2CO3, MeOH, reflux; (b) H2O; (c) HSCH2CO2Me, Et3N, MeOH, reflux; (d) HSCH2CO2Me, Et3N, HPMA, DMF,
room temperature; (e) NaOMe, MeOH, reflux; (f) Zn, CaCl2, H2O, MeOH, reflux.
intermediate that hydrolysed during column chromato-
graphy. Similar situations were encountered in our earlier
work.17 Compound 15 has been prepared by nitrating
4-methoxybenzaldehyde,30 by treating (4-methoxy-3,5-
dinitrophenyl)methanol with formaldehyde in aqueous
methanol containing sodium hydroxide31 and by heating
4-bromo-3,5-dinitrobenzaldehyde in methanolic sodium
methoxide.22a,32 The reaction of 13 with methyl thio-
glycolate and triethylamine in N,N-dimethylformamide
gave the tele substitution product 16 in 52% yield, without
any trace of the corresponding aldehyde.
by heating 3-cyanobenzoic acid in a mixture of phenyl-
phosphonic dichloride and phosphorus pentachloride
(Scheme 5). This is a general method given in a
patent18 where only the elemental analysis of the
compound is given. One other method of preparing 18 is
known, namely, photochlorination of 3-methylbenzo-
nitrile.33
Heating compound 18 in methanol containing one equiva-
lent of sodium methoxide afforded 5-dichloromethyl-2-
methoxybenzonitrile 19, a product of tele nucleophilic
substitution. Surprisingly, the reaction of 18 with methyl
thioglycolate and triethylamine afforded 20, a product of a
classical SNAr reaction. To our knowledge this represents
the first nucleophilic displacement of cyanide from a
benzene derivative.
Since the cyano group is somewhat less electron-withdraw-
ing than the nitro group it was of interest to ascertain
whether 3-trichloromethylbenzonitrile 18 would undergo
tele nucleophilic substitution. Compound 18 was prepared
Scheme 4. Reagents: (a) PhP(O)Cl2, PCl5, 50ЊC, reflux; (b) MeONa, MeOH, room temperature; (c) HSCH2CO2Me, Et3N, DMF, 120ЊC.

450
T. Giannopoulos et al. / Tetrahedron 56 (2000) 447–453
Scheme 5. Reagents: (a) PhP(O)Cl2, PCl5; (b) MeONa, MeOH, reflux; (c) HSCH2CO2Me, Et3N, EtOH, reflux.
Reactions of compounds 2, 13 and 18 with sodium phen-
oxide or thiophenol/triethylamine failed. Standard reactions
with a variety of carbon and phosphorus nucleophiles and
with sodium or potassium azide were also unsuccessful. In
the above reactions starting material was recovered except
for the reaction with azide which gave unrecognisable
products.
was added in one portion and the mixture was heated
under reflux for 15 h. The excess of phosphorus oxychloride
was distilled off and the oily residue was poured slowly into
a cold aqueous 10% sodium carbonate solution (45 mL) and
then extracted with chloroform ꢀ3×15 mL† and dried
(Na2SO4). The solvent was removed in vacuo and the resi-
due was purified by flash chromatography (light petroleum)
to give the title compound 2 (0.733 g, 50%) as a yellow oil
(lit.19a bp 128ЊC/1 mmHg); nmax(Nujol) 1530, 1350 cmϪ1
;
dH (400 MHz; CDCl3) 7.60 (1 H, t, Jˆ8.1 Hz, H-5), 8.16–
8.24 (2 H, m, H-4 and H-6), 8.72 (1 H, s, H-2); m/z (EI) 239
(4, Mϩ), 204 (100), 158 (20), 122 (32), 73 (8%).
Experimental
General methods
Reaction of 1-nitro-3-trichloromethylbenzene with meth-
oxide. To a stirred solution of 1-nitro-3-trichloromethyl-
benzene (0.3 g, 1.2 mmol) in dry methanol (15 mL), was
added a solution of sodium methoxide (0.067 g, 1.2 mmol)
in dry methanol (5 mL). The mixture was heated under
reflux for 24 h. The solvent was removed in vacuo and the
residue purified by flash chromatography (8% ethyl acetate/
light petroleum). Two fractions were obtained. The first
fraction gave 4-methoxy-3-nitrobenzaldehyde 6 (0.128 g,
59%) as pale yellow microcrystals, mp 82–84ЊC (lit.22d
Melting points were taken on a Bu¨chi 510 apparatus and are
uncorrected. Infrared spectra were recorded on a Perkin–
Elmer 257 spectrometer, solids as Nujol mulls and liquids as
thin films between sodium chloride discs. Elemental
analyses were performed on a Carlo Erba 1106 elemental
analyser. Nuclear magnetic resonance spectra were
measured at 300 MHz on a Bru¨ker AC 300 spectrometer
or at 400 MHz on a Bru¨ker AMX 400 spectrometer using
tetramethylsilane as internal standard. Mass spectra were
obtained by use of Finnigan 4500 (low resolution) or
JEOL JMS-AX 505W (high resolution) instruments using
EI or CI (NH3). Data are given for ions containing 35Cl only.
Appropriate isotope patterns were observed.
mp 81–83ЊC); nmax(liquid film) 3100, 1535, 1350 cmϪ1
;
dH (400 MHz; CDCl3) 4.04 (3 H, s, Me), 7.24 (1 H, d,
Jˆ7 Hz, H-5), 8.07 (1 H, d, Jˆ7 Hz, H-6), 8.31 (1 H, s,
H-2), 9.90 (1 H, s, CHO); m/z (EI) 181 (9, Mϩ), 150 (55),
135 (4), 104 (12), 78 (10); HRMS (EI): Mϩ found 181.0368.
C8H7NO4 requires 181.0375. The second fraction gave
methyl 3-nitrobenzoate 4 (0.05 g, 23%), identical to an
authentic sample.
All reactions were carried out under argon. Analytical TLC
was carried out on Fluka silica gel 60 F254. Preparative flash
chromatography was carried out using Merck 9385 silica
gel. Light petroleum refers to the fraction with bp 40–
60ЊC. Solvents and reagents were used as received from
the manufacturers except for dichloromethane, ethanol,
ethyl acetate, methanol and light petroleum that were
dried and purified according to recommended procedures.34
Reaction of 1-nitro-3-trichloromethylbenzene with
methyl thioglycolate. Method A: To a stirred solution of
1-nitro-3-trichloromethylbenzene (0.3 g, 2 mmol) in dry
methanol (20 mL) was added methyl thioglycolate
(0.11 ml, 1.2 mmol) and triethylamine (0.25 mL,
1.8 mmol). The mixture was heated under reflux for 48 h.
The solvent was removed in vacuo and the residue purified
by flash chromatography (7% light petroleum/toluene). Two
fractions were obtained. The first fraction gave starting
material 2 (0.051 g, 18%). The second fraction gave methyl
(4-dichloromethyl-2-nitrophenylsulfanyl)acetate 7 (0.12 g,
32%) as pale yellow oil; [Found: C, 38.72; H, 3.18; N,
1-Nitro-3-trichloromethylbenzene (2). A stirred mixture
of 3-nitrobenzoic acid (1 g, 6 mmol) and phenylphosphonic
dichloride (0.82 mL, 6.6 mmol) was warmed to 50ЊC.
Phosphorus pentachloride (3.12 g, 15 mmol) was added
portionwise with care while the mixture was thoroughly
stirred. When about half of the phosphorus pentachloride
was added and evolution of hydrogen chloride gas had
subsided, the remainder of the phosphorus pentachloride

T. Giannopoulos et al. / Tetrahedron 56 (2000) 447–453
451
4.19. C10H9Cl2NO4S requires C, 38.84; H, 2.93; N, 4.53%];
nmax(liquid film) 1740, 1510, 1355 cmϪ1; dH (300 MHz;
CDCl3) 3.76 (3 H, s, Me), 3.81 (2 H, s, CH2), 6.74 (1 H, s,
CHCl2), 7.60 (1 H, dd, Jˆ8.1, 4.7 Hz, H-6), 7.81 (1 H, d,
Jˆ8.1 Hz, H-5), 8.42 (1 H, s, H-3); dC (90 MHz, CDCl3)
35.04, 53.03, 69.48, 123.93, 127.41, 129.58, 131.38, 137.87,
138.61, 168.94; m/z (EI) 309 (5, Mϩ), 274 (12), 195 (18),
150 (100), 84 (100), 76 (65%).
3-Oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxalde-
hyde (11). Zinc powder (0.56 g, 9 mmol) was added
portionwise to a stirred solution of methyl (4-dichloro-
methyl-2-nitrophenylsulfanyl)acetate (0.2 g, 0.6 mmol)
and calcium chloride (0.1 g, 0.9 mmol) in 80% aqueous
methanol (15 mL). The suspension was heated under reflux
for 2 h, cooled to room temperature and filtered. The filtrate
was diluted with water (15 mL) and extracted with chloro-
form ꢀ3×10 mL†: The combined organic layers were dried
(Na2SO4) and concentrated under reduced pressure. The
residue was purified by flash chromatography (8% ethyl
acetate/light petroleum). Two fractions were obtained. The
first fraction gave starting material 7 (0.03 g, 16%). The
second fraction gave the title compound 11 (0.065 g, 52%)
as a yellow oil; nmax(liquid film) 3210, 1705, 1665 cmϪ1; dH
(400 MHz; CDCl3) 3.71 (2 H, s, CH2), 4.66 (1 H, s, NH),
7.49 (1 H, d, Jˆ7.2 Hz, H-8), 7.57 (1 H, d, Jˆ7.2 Hz, H-7),
7.91 (1 H, s, H-5), 9.98 (1 H, s, CHO); m/z (EI) 193 (76,
Mϩ), 164 (68), 136 (42), 69 (100), 45 (59%); HRMS (EI):
Mϩ, found 193.0192. C9H7NO2S requires 193.0197.
Method B: To a stirred solution of 1-nitro-3-trichloro-
methylbenzene (0.2 g, 0.8 mmol) and methyl thioglycolate
(0.1 mL, 1 mmol) in dry methanol (15 mL) was added a
solution of potassium carbonate (0.276 g, 2 mmol) in dry
methanol (5 mL). The mixture was heated under reflux for
48 h. The solvent was evaporated under reduced pressure
and to the residue water (15 mL) was added and the mixture
extracted with dichloromethane ꢀ3×5 mL† and dried
(Na2SO4). After removal of the solvent in vacuo the residue
was purified by flash chromatography (7% light petroleum/
toluene). Three fractions were obtained. The first fraction
gave starting material 2 (0.048 g, 25%). The second
fraction gave methyl (4-dichloromethyl-2-nitrophenyl-
sulfanyl)acetate 7 (0.03 g, 12%), identical in all respects
to compound 7 described in Method A. The third fraction
1,3-Dinitro-5-trichloromethylbenzene (13).
A stirred
mixture of 3,5-dinitrobenzoic acid (5 g, 24 mmol) and
phenylphosphonic dichloride (3.7 mL, 26 mmol) was
warmed to 50ЊC. Phosphorus pentachloride (12.5 g,
60 mmol) was added portionwise with care over 1 h while
the mixture was thoroughly stirred. Evolution of hydrogen
chloride gas occurred throughout the addition. The resulting
solution was heated under reflux for 15 h, and then phos-
phorus oxychloride was distilled off. The oily residue was
poured into 20% aqueous sodium carbonate (200 mL) and
the mixture was extracted with chloroform ꢀ3×40 mL† and
dried (Na2SO4). The solvent was removed in vacuo and the
residue was recrystallised from N,N-dimethylformamide
and water to give the title compound 13 (4.56 g, 75%) as
pale yellow needles, mp 76–77ЊC (lit.29 mp 76.5–77.5ЊC);
nmax(Nujol) 1515, 1350 cmϪ1; dH (400 MHz; CDCl3) 9.13
(2 H, s, H-4, H-6), 9.25 (1 H, s, H-2); m/z (EI) 284 (25, Mϩ),
249 (100), 233 (40), 199 (10), 183 (35), 167 (36), 143 (44),
107 (42), 72 (20%).
gave methyl (4-formyl-2-nitrophenylsulfanyl)acetate
9
(0.13 g, 27%) as pale yellow oil; nmax(liquid film) 1740,
1715, 1510, 1355 cmϪ1; dH (400 MHz; CDCl3) 3.53 (3 H,
s, Me), 3.70 (2 H, s, CH2), 7.62 (1 H, dd, Jˆ8.2, 4.8 Hz,
H-6), 7.99 (1 H, d, Jˆ8.2 Hz, H-5), 8.62 (1 H, d, Jˆ4.8 Hz,
H-3), 9.93 (1 H, s, CHO); m/z (CI, NH3) 273 [100,
(MϩNH4)ϩ], 252 (32), 228 (10), 178 (12%); HRMS (CI):
(MϩNH4)ϩ, found 273.0542. C10H13N2O5S requires
273.0544).
Method C: A mixture of 1-nitro-3-trichloromethylbenzene
(0.3 g, 1.2 mmol), methyl thioglycolate (0.11 mL, 1.2 mmol)
and triethylamine (0.25 mL, 1.8 mmol) in dry N,N-dimethyl-
formamide (5 mL) and hexamethylphosphoric triamide
(0.1 mL) under argon, was stirred at room temperature for
24 h. The mixture was poured onto ice-water (25 mL) and
extracted with ethyl acetate ꢀ3×10 mL†: The combined
organic layers were dried (Na2SO4) and concentrated
under reduced pressure. The residue was purified by flash
chromatography (7% light petroleum/toluene). Two frac-
tions were obtained. The first fraction gave starting material
2 (0.054 g, 18%). The second fraction gave methyl
(4-dichloromethyl-2-nitrophenylsulfanyl)acetate 7 (0.21 g,
67%), identical to compound 7 described in Method A.
4-Methoxy-3,5-dinitrobenzaldehyde (15). To a stirred
solution of 1,3-dinitro-5-trichloromethylbenzene (0.3 g,
1.2 mmol) in dry methanol (15 mL), was added a solution
of sodium methoxide (0.071 g, 13 mmol) in dry methanol
(5 mL). Stirring was continued for 24 h at room temperature
and then the solvent was removed in vacuo. The residue was
purified by flash chromatography (8% ethyl acetate/light
petroleum) to give the title compound 15 (0.15 g, 55%) as
colourless needles, mp 86–87ЊC (lit.32 mp 87ЊC); [Found: C,
42.53; H, 2.88; N, 11.34. C8H6N2O6 requires C, 42.50; H,
2.70; N, 11.42%]; nmax(Nujol) 1690, 1550, 1370 cmϪ1; dH
(400 MHz; CDCl3) 3.99 (3 H, s, Me), 9.10 (2 H, d,
Jˆ2.1 Hz, H-2 and H-6); 9.20 (1 H, t, Jˆ2.1 Hz, CHO);
m/z (CI, NH3) 278 [100, (MϩNH4ϩ2NH3)ϩ], 218 (12),
167 (5), 148 (10), 134 (39), 108 (15), 78 (10%).
4-Dimethoxymethyl-1-methoxy-2-nitrobenzene (10). To
a stirred solution of methyl (4-dichloromethyl-2-nitro-
phenylsulfanyl)acetate (0.49 g, 1.6 mmol) in dry methanol
(15 mL), was added sodium methoxide (0.43 g, 8 mmol).
The mixture was heated under reflux for 10 h. The solvent
was evaporated in vacuo and the residue was purified by
flash chromatography (25% ethyl acetate/light petroleum) to
give the title compound 10 (0.1 g, 28 %) as an oil;
nmax(liquid film) 1520, 1335 cmϪ1; dH (400 MHz; CDCl3)
3.24 (6 H, s, OMe2), 3.88 (3 H, s, OMe), 5.30 (1 H, s, CH),
7.20 (1 H, d, Jˆ7.5 Hz, H-4), 7.85 (1 H, d, Jˆ7.5 Hz, H-5),
8.46 (1 H, s, H-2); m/z (EI) 227 (37, Mϩ), 196 (100), 180
(14), 149 (46), 121 (75), 77 (28%); HRMS (EI): Mϩ, found
227.0820. C10H13NO5 requires 227.0794.
Reaction of 1,3-dinitro-5-trichloromethylbenzene with
methyl thioglycolate. To a stirred solution of 1,3-dinitro-
5-trichloromethylbenzene (0.3 g, 1.2 mmol) and methyl
thioglycolate (0.1 ml, 1.3 mmol) in dry N,N-dimethylforma-
mide (15 mL), was added dropwise a solution of triethyl-
amine (0.3 mL, 2 mmol) in dry N,N-dimethylformamide

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T. Giannopoulos et al. / Tetrahedron 56 (2000) 447–453
(5 mL). The resulting mixture was heated at 120ЊC for 10 h
after which it was cooled to 0ЊC. Water (50 mL) was added
and the mixture extracted with ethyl acetate ꢀ3×15 mL† and
diethyl ether ꢀ3×15 mL†: The combined extracts were dried
(Na2SO4) and the solvents evaporated. The residue was
purified by flash chromatography (25% ethyl acetate/light
petroleum) to give starting material 13 (0.06 g, 20%) and
methyl (4-dichloromethyl-2,6-dinitrophenylsulfanyl)acetate
16 (0.22 g, 52%) as a yellow oil; [Found: C, 33.72; H, 2.19;
N, 7.94. C10H8Cl2N2O6S requires C, 33.90; H, 2.28; N,
7.91%]; nmax(liquid film) 1740, 1550, 1370 cmϪ1; dH
(400 MHz; CDCl3) 3.72 (3 H, s, Me), 3.81 (2 H, s, CH2),
6.76 (1 H, s, CHCl2), 9.13 (2 H, s, H-4, H-6); m/z (EI) 355
(15, MHϩ), 329 (38), 307 (100), 289 (73), 256 (18), 210
(35%).
light petroleum) to give the title compound 20 (0.116 g,
30%) as a colourless oil; [Found: C, 39.97; H, 3.29.
C10H9Cl3O2S requires C, 40.28; H, 3.04%]; nmax(liquid
film) 1740 cmϪ1; dH (400 MHz; CDCl3) 3.52 (3 H, s, Me),
3.68 (2 H, s, CH2), 7.54 (1 H, t, Jˆ7.9 Hz, H-5), 7.65 (1 H,
d, Jˆ7.9 Hz, H-4), 8.09 (1 H, d, Jˆ7.9 Hz, H-6), 8.15 (1 H,
s, H-2); dC (90 MHz, CDCl3) 41, 52, 67, 112, 117, 129, 129,
129, 133, 145, 169; m/z (EI) 298 (5, Mϩ), 268 (42), 219 (15),
184 (100), 114 (30%).
Acknowledgements
This work was supported by grants from the Research
Committee of the University of Ioannina and the General
Secretariat of Research and Technology, Athens (to T.G.)
and by a CASE award from the UK SERC in conjunction
with AstraZeneca Agrochemicals (to J.R.F.). We are par-
ticularly grateful to Dr. D. Cartwright for his continuous
support and, A. Cakebread and R. Tye for mass spectra
obtained on a machine funded by the University of London
Intercollegiate Research Services Scheme.
3-Trichloromethylbenzonitrile (18). A mixture of 3-cyano-
benzoic acid, (5 g, 34 mmol) and phenylphosphonic
dichloride (10.2 mL, 68 mmol) was heated to 60ЊC and stir-
red as phosphorus pentachloride (25 g, 115 mmol) was
added in portions until evolution of hydrogen chloride
slowed and the mixture became clear. The remainder of
the phosphorus pentachloride was then added in a single
portion and the mixture was heated under reflux for 16 h.
The excess of phosphorus oxychloride was distilled off and
the oily residue was poured slowly onto crushed ice
(300 mL). The resulting mixture was neutralised with
potassium carbonate and then extracted with chloroform
ꢀ3×100 mL†: The combined extracts were dried (MgSO4),
the solvent was evaporated, and the residue was distilled at
155ЊC/6 mmHg to give the title compound 18 (6.8 g, 91%)
as a colourless oil (lit.33a bp 74–76ЊC/0.1 mmHg); nmax(Nu-
jol) 2180 cmϪ1; dH (300 MHz; CDCl3) 7.56 (1 H, t, Jˆ8 Hz,
H-5), 7.67 (1 H, d, Jˆ8 Hz, H-6), 8.13 (1 H, d, Jˆ8 Hz, H-
4), 8.17 (1 H, s, H-2); m/z (CI) 220 (80, MHϩ), 184 (100),
114 (45%).
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